The present invention is in the field of transmucosal delivery devices used to deliver drugs or other active agents across mucosal tissues. More particularly, the present invention involves dissolvable transmucosal delivery devices that can be used to isolate a drug or other active agent against a mucosal layer but which will dissolve or otherwise disintegrate over time when exposed to moisture (e.g., saliva).
The Relevant Technology
Oral mucosal drug delivery is an alternative method of systemic drug delivery. It offers several advantages over both injectable and enteral delivery. Drugs absorbed via the oral mucosa avoid the low pH gastric fluid and proteases, as well as first-pass metabolism in the liver. The onset of action is faster than oral administration. Unlike injections, oral transmucosal delivery is non-invasive and not painful. Moreover, a patient can administrer the medicine without help from a medical professional.
There is considerable interest in developing new dosage forms that can deliver drugs and other active agents across the oral mucosa of humans and other living things. In general, oral transmucosal dosage forms can be classified in one of three categories: (1) solid forms, (2) gum, and (3) patches. Examples of common solid dosage forms include lozenges, lozenges on a stick (e.g., lollipops), buccal tablets, and sublingual tablets. As the solid matrix dissolves or otherwise disintegrates in the oral cavity it releases the drug, which is absorbed by the oral mucosa. This type of dosage form is referred to as an “open system” because saliva can flow freely to and from the dosage form to dissolve or otherwise disintegrate the formulation. Drug concentration is generally controlled by how fast the matrix dissolves or otherwise disintegrates, which is controlled by how fast the patient sucks the unit.
Gum, like lozenges and tablets, is an open system. When this dosage form is chewed the drug is released from gum into the oral cavity where it can be absorbed by oral mucosa. Drug release from gum is controlled by the make up of the delivery device, as well as how fast the gum is chewed. In general, gum dosage forms last longer than lozenges or tablets.
The term “buccal patch” typically refers to a flexible film that adheres to the oral mucosa and delivers a drug over a period of time. The buccal patch dosage form can be further divided into three types or subcategories: (1) dissolvable matrix patches, (2) patches having a non-dissolvable backing, and (3) patches with a dissolvable backing. For examples known in the art of buccal patch technology see U.S. Pat. No. 3,598,122; U.S. Pat. No. 3,972,995; U.S. Pat. No. 4,517,173; U.S. Pat. No. 4,573,996; U.S. Pat. No. 4,572,832; U.S. Pat. No. 4,704,119; U.S. Pat. No. 4,713,243; U.S. Pat. No. 4,715,369; U.S. Pat. No. 4,740,365; U.S. Pat. No. 4,855,142; U.S. Pat. No. 4,876,092; U.S. Pat. No. 4,900,552; U.S. Pat. No. 4,900,554; U.S. Pat. No. 5,137,729; U.S. Pat. No. 5,298,256; U.S. Pat. No. 5,346,701; U.S. Pat. No. 5,516,523; U.S. Pat. No. 5,578,315; U.S. Pat. No. 5,599,554; U.S. Pat. No. 5,639,469; U.S. Pat. No. 5,766,620; U.S. Pat. No. 5,800,832; U.S. Pat. No. 5,863,555; U.S. Pat. No. 5,900,247; U.S. Pat. No. 6,159,498; U.S. Pat. No. 6,210,699; and U.S. Pat. No. 6,319,510.
Dissolvable matrix patches work similar to gum, lozenge and tablet dosage forms. The dissolving matrix releases the drug into the oral cavity for absorption by oral mucosa. They usually last longer than lozenges or tablets. Unlike gum, dissolvable matrix patches release the drug passively rather than actively. One limitation of all these systems is that the drug concentration is not well controlled.
In order to control the drug concentration over the period of drug delivery, buccal patches with backings were developed. Controlling drug concentration is particularly important when mucosally delivering drugs that require the help of permeation enhancers. Permeation enhancers are chemicals that can temporarily compromise the integrity of the oral mucosa so that drug delivery can be enhanced. The concentration of enhancers needs to be carefully controlled. If the concentration is too high, the enhancer can cause mucosal irritation or damage. If too low, it may not provide the desired enhancement of drug delivery. One way to maintain control of both drug and enhancer concentration is to include a backing so that the active formulation of the buccal patch is completely isolated from the surrounding environment.
There are two types of backing systems in the buccal patch dosage form: dissolvable and non-dissolvable. Non-dissolvable backings are usually flexible. They are designed to stay in the oral cavity for long periods of time, e.g., up to 10-15 hours. The disadvantage is that the patch has to be removed from oral mucosa by the patient after drug administration.
Patches with dissolvable backings are designed to stay in the oral cavity for a short period of time. It is intended for the backing to control the local environment inside the patch so that high efficient drug delivery can be achieved in a controlled fashion. Over time, it is intended for the backing to dissolve or disintegrate in the oral cavity (e.g., when exposed to saliva) in order for all or part of the delivery device to go away. This eliminates the need to remove the patch after treatment is complete.
One of the challenges of providing patches with a dissolvable or disintegratable backing has been the need to provide materials that are able to provide an adequate barrier while still being able to dissolve or disintegrate over time. Another challenge inherent in transmucosal delivery of drugs or other active agents, particularly within the oral cavity, is the need to isolate and maintain the drug or other active agent against the mucosal layer. Otherwise, the active agent may diffuse into the oral cavity where it can inadvertently or deliberately be swallowed or expectorated from the mouth. In either case, the drug or other active agent will not be able to pass through the mucosal membrane as intended. The challenge, therefore, is to provide a transmucosal delivery device that is able to both isolate and maintain a drug or other active agent against the mucosal surface while also being able to dissolve over time in the presence of moisture.